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Nanoscale ; 16(21): 10306-10317, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38727538

RESUMO

As a highly contagious opportunistic pathogen, Pseudomonas aeruginosa (P. aeruginosa) is one of the main causes of healthcare-associated infections. The drug-resistant nature of P. aeruginosa can render antibiotic treatments ineffective, leading to a high morbidity and mortality. Higher specificity and reduced toxicity are features of immunotherapy, which can generate robust immune responses and preserve long-term immunological memory to completely eradicate infections. In this study, we developed a type of P. aeruginosa vaccine based on a metal-organic framework. Specifically, MIL-101-Al nanoparticles were synthesized to encapsulate antigens derived from the bacterial lysate (BL) of PAO1, a drug-resistant P. aeruginosa, and the adjuvant unmethylated cytosine-phosphate-guanine oligonucleotide (CpG), which were then modified with palmitic acid (PAA) to obtain MIL-BC@PAA. The stability and biocompatibility were significantly increased by capping with PAA. Moreover, MIL-BC@PAA showed significantly enhanced uptake by antigen presenting cells (APCs), and promoted their maturation. Importantly, immunity studies revealed the greatly elicited antigen-specific humoral and cellular responses, and a protection rate of about 70% was observed in P. aeruginosa-challenged mice. Overall, these results demonstrate the promising potential of MIL-BC@PAA as an ideal nanovaccine for P. aeruginosa vaccination.


Assuntos
Adjuvantes Imunológicos , Estruturas Metalorgânicas , Ácido Palmítico , Infecções por Pseudomonas , Pseudomonas aeruginosa , Pseudomonas aeruginosa/imunologia , Pseudomonas aeruginosa/efeitos dos fármacos , Animais , Camundongos , Infecções por Pseudomonas/imunologia , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/prevenção & controle , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Adjuvantes Imunológicos/química , Adjuvantes Imunológicos/farmacologia , Ácido Palmítico/química , Feminino , Nanopartículas/química , Camundongos Endogâmicos BALB C , Oligodesoxirribonucleotídeos/química , Oligodesoxirribonucleotídeos/farmacologia
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